Guanyl and biguanyl compounds



2,213,474 GUANYL AND BIGUANYL COMPOUNDS Bruno Puetzer, Albany, N. Y., assignor to Winthrop Chemical Company, Inc., a corporation of NewYork N Drawing. Original application December 14,

1934, Serial No. 757,547. Divided and this application April 20, 1937, Serial No. 138,063. In Germany December 16, 1933 Claimsw (Cl. 260-564) display a bactericidal action.

In accordance with the present invention products displaying a bactericidal action are obtainlecular cyanamides'containing an aliphatic radical of from 11 to about 16 carbon atoms with ammonia, amines, guanidines or their salts. Dodecylcyanamide, for instance, yields with ammonia dodecylguanidine and with guanidlne 5 able by the manufacture of guanyland biguanyl dodecylbiguanide.

compounds wherein the carbon atom of the The above mentioned higher aliphatic radicals guanyl group C(=NH)NH2 or the one carbon of from about to about 16 carbon atoms may atom of the biguanyl group be saturated or unsaturated and may contain substituents. such as the hydroxy, alkoxy and amino 10 C( NH)NHC( NH) NHZ group. The carbon chain of the higher aliphatic is connected by an amino group with a higher radical may be interrupted by other members or ali hatic radical containing from about 10 to r up r in tanc an ether-lik bo nd oxy about 16 carbon atoms. or sulfur group, by amino groups or even by cyclic In accordance with the present invention the E UPS- -A y c group y also be pa O the said new guanyland biguanyl compounds are connecting member between the guanyl radical obtained, for instance,- by condensation of a a d the higher alipehtie radical- The amino higher primary or secondary aliphatic amine congroups Of the u y d b uany r dic y taining the aliphatic radical of from about 10 to e t ut d y yl up The amino groups about 16 carb n at m with y id dicyanof the guanyl radical may also be connected with diamide or with an alkyor arylalkylether of One a o er y an kylene gr p, t the isourea, isothiourea, guanylisourea or guanyl guanyl gro p is a member of heteroeyelie isothiourea. The components may also be used 0191154 in the form of their salts with acids. The con- The w guanyl and ny c mp r densation of cyanamide with a primary aliphatic a ly Crysta line products. I the form 0f the amine proceeds, for instance, in accordance with free bases they are Practically insoluble in W e the f ll wi equation: but soluble in organic solvents, such as alcohols,

ether, acetone and the like. In the form of their salts with mineral acids, for instance, the hydro- H halic acids, sulfuric acid and nitric acid, as well as,

in the form of their salts with organic acids, such g f gt gi s igg gggigg g igigfggg g as acetic, lactic, citric and benzoic acid, the new Compound. products are soluble in water and in alcohol but i insoluble in ether. In view of their excellent H'3C-(CI-Ig)15-NH2+ bactericidal activity the new products. may be 5 NEC NH C(=NH) N used for instance as antiseptics, further for outer H3C(CH2)15-NHC(=NH) disinfections, for instance, for the disinfection of N medical instruments, bandages and the like.

' Since the new compounds likewise display a con- T eondensetlen between t l allphatle siderable wetting-, foamingand dispersing acno n an c y th r p s tion,'they may likewise find application as disl h e Sp Off a y mereeptanelll the fellOW- infecting cleaning agents. Because of the above mg manner? specified properties the new compounds are also suitable as additions to cosmetica, such as face c ip "7 s lotions, gargles and the like. They may also HscwHz) =NH) NHz+a1ky1 sH serve as a means to dissolve Water-insoluble sub- I stances, such as medicines, ethereal oils and the T e other condensations referfed to above like. Because of their bactericidal action they are us in if ilarlman also suitable as preserving agents.

' Instead of :the higher aliph tic l h l and The invention is further illustrated by the folmercaptanes their reactive esters likewisemay be lowing examples Without being restricted theletoi used inthis reaction; for instance, the esters with Example grams f d ylamine, 10 the hydrohalic acids and with aromatic sulfonic j s. f alcohol andms f t y soacids. Such esters may be reacted with guanithiourea-hydrobromide are heated in the waterdine, biguanidine or with .the salts of the said bath for, 6. hours. After cooling the separated compounds. Cetylbromide, for instance, reacts crystals are filtered with u i W ed With alwith guanidine with the formation of cetylguanicohol and ether and recrystallized from alcoholy m i ether. The hydrobromide of n-dodecylguanidine I The new guanyland biguanyl compounds may .thus obtained forms colorless crystals melting at be further obtained by reacting upon higher mo- 82 C. It is soluble in water and has soap-like properties. The free n-dodecylguanidine crystallizes from a mixture of benzene and petroleum ether in colorless crystals melting at 96 C.

Example 2.9.3 grams of dodecylamine, 6 ccs. of water and 10.9 grams of S-ethylguanylisothiourea-hydrobromide (colorless crystals melting at 164 C. obtained by treating guanylthiourea with ethylbromide in alcoholic solution) are heated on the water-bath until the formation of bubbles has ceased. The ethylmercaptane formed is distilled off in vacuo, the residue dissolved in water, the solution rendered alkaline and extracted with ether. On drying the ether and evaporation, the dodecylbiguanide separates in colorless crystals melting at 96 C. ,It forms a pink colored copper complex salt melting at 219 C. Its solution in the calculated quantity of dilute hydrochloric acid has soap-like properties.

Example 3.-5 grams of aminoethyl-dodecylsulfide (boiling at 156 C. under 3 mm. pressure, melting at 265 C. obtained from dodecylmercaptane and amincethylbromide), 2 cos. of alcohol and 3.8 grams of S-ethylisothiourea-hydrobromide are heated in the Water-bath for 20 minutes. After the reaction mixture has been dissolved in ether it is filtered and cooled with an ice-common salt mixture. The dodecylthioethyl-guanidinhydrobromide crystallizes in colorless crystals melting at 58 C. It has soap-like properties.

Example 4.-6.2 grams of aminoethyldodecylsulfide, 2 cos. of alcohol and 5.5 grams of S-ethylguanylisothiourea-hydrobromide are heated on the water-bath for half an hour. After the addition of ether the mixture is filtered and cooled with an ice-common salt mixture. After standing for a longer period of time the dodecyl-thioethylbiguanid-hydrobromide crystallizes in colorless crystals melting at C. It has soap-like properties.

Example 5.-23 grams of m-aminophenyldodecylether-hydrochloride, cos. of water and 10 grams of dicyandiamide are heated to boiling for two hours. The reaction' mixture is dissolved with about the same quantity of methyl alcohol, filtered and the filtrate treated with excess ammonia. The precipitate separating is recrystallized from alcohol-ether. The 3-biguanidinophenyl-dodecyl-ether forms crystals melting at 207 C.

The m-aminophenyldodecylether-hydrochloride specified above as the starting material is obtained in the following manner:

42 grams of m-nitrophenol are heated to boiling in a solution of 6.9 grams of sodium in 160 ccs. of absolute alcohol and 75 grams of dodecylbromide are added drop by drop. After boiling for 7 hours the alcohol is removed by steam distillation, the residue is extracted with ether and the ethereal solution is shaken with dilute caustic potash solution, dried with potassium carbonate and evaporated. In 'the vacuum'distillation of the ether residue the m-nitrophenyldodecylether distils under 0.5 mm. pressure at 189 C. After cooling it forms light yellow crystals melting at 43 C. By reduction with stannous chloride and hydrochloric acid the m-aminophenyldodecylether, boiling at 204 C. under 0.5 mm. pressure, is obtained which forms colorless crystals melting at 63 ,C. Its hydrochloride forms colorless '10 crystals melting at C.

Example 10.--10 grams of S-methylisothioethyleneurea-hydroiodide, 50 grams of amyl alcohol and 15.2 grams of dodecylamine are heated It has the following fomula:

CHr-N o-naoun and melts at 86 C.

This application is a division of my copending application for Letters Patent Serial No. 757,457, filed December 14, 1934, now U. S. Patent 2,156,- 193, issued April 25, 1939.

I claim:

1. A compound selected from the group consisting of mono-guanyl and mono-biguanyl compounds in which a carbon atom of a group selected from the group consisting of the guanyl and biguanyl group is connected with an aliphatic radical of from 10 to 16 carbon atoms by means of an amino group.

2. A compound selected from the group consisting of mono-guanyl and mono-bi-guanyl compounds selected from compounds of the class consisting of compounds of the formulae NH-R R-NH-C and wherein R stands for an aliphatic radical containing 10 to 16 carbon atoms selected from the group consisting of hydrocarbon radicals and of aliphatic radicals containing oxygen as a member of the aliphatic chain and containing sulfur as a member of the aliphatic chain, R1 stands for a substituent selected from the group con ,sisting of hydrogen, alkyl and the guanyl group,

R2 stands for a substituent selected from the group consisting of hydrogen and alkyl and alk stands for an alkylene group.

3. A compound selected from the group consisting of mono-guanyl and mono biguanyl compounds of the formula at 96 C., in the form of its hydrobromide at 82 C.

BRUNO PUETZER. 

